AMERICAN JOURNAL OF SCIENTIFIC AND INDUSTRIAL RESEARCH

2010, Science Hu, http://www.scihub.org/AJSIR

ISSN: 2153-649X

Mathematical modeling of Hepatitis C Virus transmission among injecting

drug users and the impact of vaccination
I. K. Dontwi1, N. K. Frempong1, D.E. Bentil2, I. Adetunde3 and E. Owusu-Ansah1
1

Department of Mathematics, Nkrumah University of Science

and Technology Kumasi, Ghana
2
Department of Mathematics and Statistics, University of Vermont, Burlington Vermon, USA.
3
Department of Mathematics, University of Mines and Technology, Tarkwa, Ghana
ABSTRACT
In the western world, transmission of hepatitis C occurs primarily through injecting drug use.
Transmission of hepatitis C in injecting drug users is mainly associated with the sharing of
contaminated syringes/needles, although evidence for risk of hepatitis C infection through sharing of
other injecting paraphernalia is increasing. Due to the influx of hard drugs like cocaine, heroin in the
West Africa sub-region giving rise to a menace, there is the need to look at the transmission of
hepatitis C among IDUs. The mathematical model quantifies the transmission of Hepatitis C among
IDUs in the population. Results: From the compartmental models, the frequency of sharing injecting
materials has an impact on the force of infection and the prevalence of HCV. The main goal of the
vaccination program is herd immunity i.e. ensuring that no epidemic can take place.
Keywords: Force of infection, Prevalence, Hepatitis C, Injecting Drug user (IDU), Epidemic,
Vaccination, Compartmental Model.
INTRODUCTION
Hepatitis C virus (HCV) is a common cause of liver
disease and a major public health problem world
wide. In 1989, HCV was identified and the possibility
of screening blood products for contamination with
hepatitis C arose. Unfortunately, the virus had by that
time already spread through large parts of the worlds
population and had established itself as a leading
cause of severe liver disease (Di Bisceglie, 1998).
The features of HCV infection that make it hard to
combat are that a large fraction of all infected
individuals become chronic carriers of the virus.
About 170 million people are chronically infected with
HCV worldwide (Kretzschmar and Wiessing, 2006).
Acute infection is rarely diagnosed and information
about the clinical cause of HCV infection has come
largely from retrospective studies of patients with
established liver disease. Such studies exclude
people with no clinical evidence of infection and
observations are often biased towards severe
disease outcomes (Kretzschmar and Wiessing, 2006)..
The strict screening procedures for blood products
have succeeded in reducing the number of new
infections in the developed world. Currently, in
industrialized countries like the US and countries in
Europe, the most important risk factor for HCV
infection is intravenous drug uses (IDUs) [2]. In this
group, transmission occurs via sharing injection
equipments such as syringes, needles and other

paraphernalia. The increased risk associated with

sharing of contaminated needles, syringes and other
modes of transmission are significant enough to
ensure a high prevalence of hepatitis C infections in
many populations of IDUs in Europe (Mathei et al.
2005). As no vaccine against HCV is currently
available, preventive measures through information
and education on the effect of needle exchange and
distribution of other paraphernalia are the only
weapons available in the fight against further spread
of HCV.
Mathematical modeling provides an alternative
means to define our problems, organize our thoughts,
understand our data, communicate and test our
understanding,
and
make
predictions.
The
deterministic compartmental model provides means
of obtaining insight into the dynamics of viral
transmission among IDUs.
A deterministic
compartmental model therefore becomes an
intellectual
tool
for
knowledge
growth
in
epidemiological data. An epidemiological parameter
of interest is the force of infection. That is the
average rate at which susceptible host become
infected. In an open population where individuals are
recruited under the assumption of life-long immunity
following initial HCV infection and that the disease is
in a steady state the force of infection can be
calculated.

Am. J. Sci. Ind. Res., 2010, 1(1): 41-46

acute infection moves out of that state with rate 1,

with a fraction becoming chronic carriers and the
remaining fraction, (1- ) recovering completely.
Chronic carrier individuals can still clear the virus with
rate 2 and move into the recovered state. Finally, by
N we denote the total population size i.e. N
=S(t)+A(t)+C(t)+R(t), assuming that the population
remains constant over time.The pictorial description
of the model in the previous page can be described
by the set of differential equations:

In this paper we focus on a deterministic

compartmental model in modeling the transmission of
Hepatitis C among injecting drug users (IDUs) in a
homogenous population. A proposed force of
infection proposed in [2] in modeling the transmission
of HCV among IDUs was adopted. The underlying
assumption is that the disease spread due to the risk
behavior of the IDUs. Also, the impact of a
vaccination program in the transmission of HCV was
investigated using the deterministic compartmental
model.

dS
= B ( + )S (t )
dt
dA
= S ( t ) ( 1 + ) A (t )
dt
dC
= 1 A ( t ) ( 2 + )C (t )
dt
dR
= (1 ) 1 A ( t ) + 2 C ( t ) R ( t )
dt

The rest of the paper is organized as follows: In

Section 2 the methodology used is discussed, results
from the compartmental model are discussed in
section 3, and a result from the impact of vaccination
is the subject of discussion under section 4.
Discussion, conclusion and recommendation are
covered in section 5 and finally, the Appendix which
contains the code used from MATHLAB.

From [2] proposed a duration-dependent force of

infection given by:
The force of infection was defined as
.. ( 1.1)
A (t)
C (t)

METHODOLOGY
Designing the Model (Stages of disease, HCV): A
compartmental model is used to represent the
dynamics of infection for HCV as shown in Figure M1
below. In the figure, the population is subdivided into
a number of subsets according to the most important
stages of HCV. In this model, four subsets are of
interest: we denote the number of susceptibles by S,
the number of acutely infected individuals by A, the
number of chronic carriers by C and the number
recovered by R. The individuals are recruited into the
susceptible class by the quantity B, and the mortality
rate (naturally) given as . The susceptible hosts are
infected by the acute infection class with a force of
infection , which depends on the rate of borrowing
injecting equipment k, and the transmission rates
(probabilities ba, bc) [2].

Sus

Chr

(1.0)

(t) = k (b

N (t)

+ b

N (t)

The above mathematical model presented by [2] was

fitted using MATLAB(). The time window was
chosen in months since disease specific parameters
and demographic parameter values are based on
monthly measurements, however a yearly time
window could be adopted. This model (1.1) was used
to calculate the duration dependent force of
infection, (t ) , with N=1 (nondimensionalized) as the
population size. For large populations, a more natural
approach may be based on proportions instead of
absolute numbers. The duration-dependent force of
infection was estimated for hepatitis C at different
contact rates of k values. In an equilibrium position,
N=B/ and
dS(t)/dt = dA(t)/dt = dC(t)/dt = dR(t)/dt = 0. The
nondimensionalization is achieved by setting
s(t)=S(t)/N, a(t)=A(t)/N, c(t)=C(t)/N, r(t)=R(t)/N. The
model then becomes:

Acu

ds
dt
da
dt
dc
dt
dr
dt

Rec

Fig M1: Flow chart of a simple HCV model (SACR).

(kb

= B
=

(kb

a ( t ) + kb

a ( t ) + kb

a (t )

= (1 )

c ( t ) )s (t

c ( t ) )s (t
+

a (t ) +

) s (t )

) (

(1.2)

)a (t )

)c (t )
c (t ) r (t )

2.2 The impact of a Vaccination program: We turn

now to discuss the impact of a possible vaccination
program which was introduced into the population.
Let us assume that at equilibrium, we introduce a
program which immunizes a proportion p of the

Here ba is the transmission probability per contact if

individual was in its primary acute infection and bc is
the transmission probability per contact if individuals
was a chronic carrier. An individual with primary

42

Am. J. Sci. Ind. Res., 2010, 1(1): 41-46

R0 is the basic reproduction number, which is the

mean number of secondary infections that is caused
by a single index throughout his/her infectious period
when introduced in a fully susceptible host. R0 is
often considered as the threshold quantity that
determines when an infection can invade and persist
in a new host population. With a deterministic model,
a pathogen with R0 > 1 in the population will always
invade the population to cause an epidemic.

population at birth, the remaining fraction (1-p) at risk

joins the susceptible class. All other conditions
remain the same. The main goal of immunization is to
ensure that no epidemic can take place since the
disease is endemic. For a model formulated in terms
of proportions with natural birth and death rates and
force of infection (t ) , the equations for the SACR
are given by

ds
dt
da
dt
dc
dt
dr
dt

= (1 p ) ( (t ) + ) s (t )

RESULTS

= (t ) s (t ) ( 1 + )a (t )

Deterministic compartmental Model: In the first

mathematical model (1.2) we used the mortality rate
in a developed country to support the model
assumptions for HCV among IDUs, with =0.001038.
In this model it is assumed that the new recruiters B
are the proportion of the population which is
equivalent to the mortality rate in a developed
country. The duration of acute phase of infection is
estimated at around two months [8]. It is estimated
that the fraction of acutely infected persons who
become chronic carriers is around 80% [9]. That is
the disease specific parameters i.e. ba, bc, 1, 2
defined in [2] were not changed i.e. ba= 0.3, bc= 0.03,
1= 5, 2=0.01 and somehow reflects reality.

(2.0)

= 1 a (t ) ( 2 + )c (t )
= (1 ) 1 a (t ) + p + 2 c (t ) r (t )

We note that the above model describe an open

population in which the flow of individuals into the
population is N. In fact, since r(t)=1-s(t)-a(t)-c(t), the
dynamical behavior of this system is fully described
by the first three equations i.e. ds/dt, da/dt and dc/dt.
Assuming the following:

a (t ) = A(t ) = Na (t )
c (t ) = C (t ) = Nc(t )
(t ) = a (t ) = c (t )

Assuming the average duration of injection

(difference between the age at first injection and the
age at test) is 10 years. From Figure 1(a) and 1(b)
the disease parameters were held constant and k
varied from 10 to 20. From figure 1(a), for k=10, one
can observe small proportions of the population who
had acute infection. Proportions of infected
individuals who are chronic carriers increases to a
peak of almost 70% of the population size within
duration of approximately 20 months and declines
somehow because of the recovery rate which is
almost 1% over a long duration. The proportion of
individuals recovering increases steadily and
becomes larger than the proportion of the carriers
after almost 60 months (5 years) over the entire
duration of exposure. Compared to figure 1(b) on the
right panel, where k is doubled to 20, at almost 12
months (a year) the dynamics are steeper for the
acute, chronic carrier and recovery states at shorter
duration of exposure. The rate of infections in each
state are higher when k=20 at shorter duration of
exposure than when k=10. This might indicate that
the frequency of sharing injecting materials have an
impact on the transmission of Hepatitis C within a
population of IDUs whiles the transmission
probabilities do not change over time or perhaps
independent.

(2.1)

From (2.1), some algebraic simplification was done to

obtain (2.2) below:

d a (t )
dA(t )
da (t )
=
= N
dt
dt
dt
(2.2)
d c (t )
dC (t )
dc(t )
=
= N
dt
dt
dt
We formulated the second, third equations in (2.0) in
terms of the force of infection given in (2.2) to obtain
this equation:

ds
= (1 p ) ( (t ) + ) s (t )
dt
d a
= ( 1 + )a (t )[ Ro s (t ) 1]
dt
dc
= 1 a (t ) ( 2 + )c(t )
dt

(2.3)

Where

R0 =

N
1 +

(2.4)

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Am. J. Sci. Ind. Res., 2010, 1(1): 41-46

1.0

Transmission of HCV,k=20

1.0

Transmission of HCV,k=10

0.6

0.8

Susceptible
Acute
Chronic
Removed

0.0

0.2

0.4

Population
0.0

0.2

0.4

Population

0.6

0.8

Susceptible
Acute
Chronic
Removed

20

40

60

80

100

120

Duration of Exposure(months)

20

40

60

80

100

Fig 1(a): Transmission for (S, A, C, R),

Fig 1(b): Transmission for (S, A, C, R),

k=20
Studying the impact of vaccination: Let us first
consider the case of no vaccination (p=0). As an
example we take a modest R0=10, 1= 5yr-1,
2=0.01yr-1 in a population with birth and death rate
=1/70yr-1. The infection is introduced with an initial
seed corresponding to 0.0001 yr-1. The time window
considered is in years.

1.0

k=10
The duration-dependent force of infection was
estimated by the model at different contact rates k.
The Figure 2 below shows the estimated forces of
infections at different values of the frequency of
sharing injecting materials, k.

0.6
0.4
0.0

0.2

Force of infection

0.8

FOI(5)
FOI(10)
FOI(15)
FOI(20)
FOI(25)

20

40

60

80

120

Duration of Exposure(months)

100

120

Duration of Exposure(months)

Fig 2: The Force of infection at different frequency of k

contacts

Fig 3(a): Susceptible with no vaccination

From figure 2, there is a very steep increase in the

force of infection at shorter durations for higher
sharing frequencies (k=25, 20). For lower sharing
frequencies i.e. k=5, 10, 15, the force of infection
rises steadily over the duration of exposed. In all
circumstances, the force of infection declines after
reaching the peak but it does not diminish to zero yet
after 120 months of exposure.

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Am. J. Sci. Ind. Res., 2010, 1(1): 41-46

settles to an equilibrium state: where s*() =1/ R0 =

0.1 and *= (R0-1) =0.1286
For the susceptible class, we introduce a program
which immunizes a proportion p=0.5 of the
population. We again look at 80% of the population
vaccinated at birth. The graphical output below
shows the impact of both vaccination program p=0.8
and p=0.5 respectively for the susceptible class.
From this graphical output, we observe that the
oscillatory frequency is lower for high vaccination
program (p=0.8) since the number of susceptibles
grows slower to the critical value (0.1) other than the
lower vaccination program (p=0.5) over a longer time
period. For s*() =1/ R0 = 0.1 which equals the
equilibrium before immunization, this value made no
reference to whether susceptibility was lost naturally
by infection or artificially by immunization. The force
of infection is calculated as:
For p=0, = (R0-1) = 0.1286 at equilibrium.
For p=0.5, () = (R0 (1-p)-1) =0.0571 < (0) =
(R0-1) =0.1286
For p=0.8, () = (R0 (1-p)-1) =0.0143 < (0) =
(R0-1) =0.1286.
We notice that the force of infection reduces when
vaccination program is conducted at early births and
further reduces for wider vaccination coverage.
The graphical output below shows the impact of both
vaccination program p=0.8 and p=0.5 respectively for
the Acute class. We observe that the frequency for
oscillation is lower for the higher vaccination program
than the lower vaccination program.

Fig 3(b): Acute class with no vaccination

We observe an initial drop in the susceptible class

from fig 3(a) and rise and fall of the acute state from
fig3 (b) that corresponds to a classical epidemic.
From fig 3(a), initial epidemic is followed by an
episode in which the pool of susceptibles is restocked
by births, during this period a new epidemic is
triggered after time approximately 15yrs when the
proportions of the susceptible is almost 20%. Fig 3(c)
in appendix demonstrates the dynamics for the
chronic carriers. We observe after time 15yrs there is
an increase of chronic infection in the population. The
second epidemic is less severe because the bulk of
the population is immune; successive epidemics are
less and less severe. In the long run, the system

Fig 4(a): Vaccination with p=0.8

Fig 4(b): Vaccination with p=0.5

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Am. J. Sci. Ind. Res., 2010, 1(1): 41-46

Fig 4(a): Vaccination with p=0.8

Fig 4(b): Vaccination with p=0.5

would be based on the rates of borrowing injecting

equipment in both groups and the fraction of needles
individuals borrow from within and between groups
respectively. The aspect of co infections with other
associated disease like HIV, whose risk may be
dependent on sharing of needles or other injecting
materials, could also be researched into.

DISCUSSION
The mathematical models fitted were presented by
(Kretzschmar and Wiessing, 2006). We assumed a
homogenous population of IDUs for the transmission of
HCV. The results show that early drug users may have
a high risk of being infected with HCV based on the
frequency of borrowing injecting materials or rates of
contacts. The force of infection for the population
varying rates of borrowing injecting materials i.e. k=1,
5,,25 also indicated that for shorter duration of
exposure, the force of infection was high.
We have also introduced a mathematical model that
looks at vaccination program for the Susceptible, Acute
infection and Chronic carriers. We observed that early
vaccination program with higher coverage of the
population reduces the force of infection thus reducing
the rates at which individuals become infected. This
helps in the slow growth of new infections, thus reducing
epidemic cycles.

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W., Alter, H.J., Schleicher, J. B., Mimms, L.T.(1992),
Lgm antibody response in acute hepatitis C viral
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Di Bisceglie, A.M. (1998), Hepatitis C. The Lancet
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Diamond ID, McDonald JM. Analysis of current status
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We see the advantage of the mathematical model as

they can be used to explore changes such as factors as
well as identify the type of data that needs to be
collected and parameters that need to be accessed.
Knowledge obtained from the mathematical model
shows that, risk groups i.e. the individuals sharing
injecting materials must be taken into account in data
collection. The duration of exposure i.e. (difference
between age at first injection and the age at test of
HCV) must also be taken into account in a data
collection.
CONCLUSION AND RECOMMENDATIONS: From a
technical point of view, changing any of the parameters
or initial conditions of the models can lead to protection
of the population through the reduction of the number of
susceptibles by immunizations, reduction of the contact
rate through public health campaigns and increase of
the removal rate through better medical treatment of the
infected individuals.
The model assumed a homogenous fixed population.
Further research is to extend the mathematical models
by including two subgroups assuming a heterogeneous
mixing pattern in the population. The mixing pattern

46